The catabolic action of insulin in the brain is mediated by melanocortins - PubMed (original) (raw)

The catabolic action of insulin in the brain is mediated by melanocortins

Stephen C Benoit et al. J Neurosci. 2002.

Abstract

Like leptin, the pancreatic hormone insulin is an important adiposity signal to the brain. We report that the hypothalamic melanocortin system is an important target of the actions of insulin to regulate food intake and body weight. Hypothalamic neurons expressing insulin receptors were found to coexpress the melanocortin precursor molecule pro-opiomelanocortin (POMC), and administration of insulin into the third cerebral ventricle of fasted rats increased expression of POMC mRNA. Finally, a subthreshold dose of the melanocortin antagonist SHU-9119 prevented the reduction in food intake caused by third-ventricular insulin administration. These data suggest that the hypothalamic melanocortin system mediates the anorexic effects of central insulin, as well as of leptin.

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Figures

Fig. 1.

Fig. 1.

Dual-label immunohistochemistry for insulin receptor-β and POMC. The top two panels_are confocal images (5 μm optical section) of ARC neurons. Positive immunoreactivity for the insulin receptor-β is depicted in_green (A), whereas POMC-positive immunoreactivity is depicted in red(B). C, An overlay of the above images. Green arrows point to single-labeled neurons; yellow _arrows_indicate dual-labeled neurons. Scale bar, 50 μm.

Fig. 2.

Fig. 2.

Hypothalamic POMC expression. POMC expression after ad libitum feeding (left bar), a 72 hr fast (middle bar), and a 72 hr fast with i3vt infusions of 4 mU of insulin every 12 hr (right bar). Central administration of insulin increased expression of POMC relative to fasting, and the resultant levels were not different from those that occurred during _ad libitum_feeding. *p < 0.05.

Fig. 3.

Fig. 3.

Effect of insulin and SHU-9119 on food intake. Mean 4 hr food intake (in grams) after i3vt administration of saline (Sal), insulin (8 mU) (Ins), SHU-9119 (0.1 nmol) (Shu), and SHU-9119 followed by insulin (S+I). SHU-9119, by itself, had no effect on food intake, whereas insulin significantly reduced intake relative to saline. Administration of SHU-9119 before administration of insulin blocked the effect of insulin to reduce food intake (*p < 0.05).

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